The worldwide prevalence of PV-infection in humans is very high. Indeed, human PVs (HPVs) are the most frequently sexually transmitted viruses of the world. See Garland, S. M. 2002. Pathology 34:213-224, which is incorporated herein my reference. Whereas nearly 100 HPV types have been described, an intensive search for animal PVs has just begun.
After infection of the basal cells of cutaneous or mucosal skin, these small DNA viruses start to induce an increased epithelial proliferation in the course of which they show a strong host- and tissue-specificity. See zur Hausen, H., and E. M. de Villiers. 1994. Annual review of microbiology 48:427-447, which is incorporated herein by this reference. A hyperproliferation of the suprabasal cells, such as the development of warts, papillomas, or condylomas, is induced by viral protein activity interfering with the pathways of cellular tumor suppressor proteins. See Chow, L. T., and T. R. Broker. 1994. Intervirology 37:150-158; and Howley, P. M., and D. R. Lowy. 2001. Fields Virology. 4th edition. Raven Press, Philadelphia. 2197-2229, which are incorporated herein by reference. These primarily benign tumors (warts, condylomas, papillomas) frequently disappear due to a cell-mediated immune response; however, some PVs contribute to malignant progression of the epithelial tumors.
In humans, 10-30% of PV-induced severe neoplasia lead to an invasive cervical carcinoma, the second most frequent cancer of women worldwide. See Einstein, M. H., and G. L. Goldberg. 2002. Cancer Investigation 20:1080-1085; and Walboomers, J. M., et al. 1999. The Journal of Pathology 189:12-19, which are incorporated herein by reference. Cervical carcinoma is believed to be entirely attributable to PV-infections and represents the most common cause of cancer mortality in women in developing countries. See Parkin, D. 2005. Presented at the 22nd International Papillomavirus Conference, Vancouver, Canada, April 30-May 6. Title: World Burden of Infection-associated Cancers; and Eder, P., I. et al. 2005. Presented at the 22nd International Papillomavirus Conference, Vancouver, Canada, April 30-May 6. Title: A new HPV DNA Test for Developing Countries, which are incorporated herein by reference. Those PVs, which demonstrate a stronger oncogenic potential are classified as high risk viruses, and can be found amongst oral, genital, and cutaneous types.
PVs have been isolated from marine mammals, including one PV isolated from skin lesions of a species of the Sirenia order, a captive Florida manatee (Trichechus manatus latirostris PV-1, TmPV-1), and from genital lesions of a species of the Cetacea order, free-ranging and captive Atlantic bottlenose dolphin (Tursiops truncates). See Bossart, G. D., R. Y. Ewing, M. Lowe, M. Sweat, S. J. Decker, C. J. Walsh, S. J. Ghim, and A. B. Jenson. 2002. Experimental and Molecular Pathology 72:37-48; Rector, A., G. D. Bossart, S. J. Ghim, J. P. Sundberg, A. B. Jenson, and M. Van Ranst. 2004. Journal of Virology 78:12698-12702; and Rehtanz, M., S.-J. Ghim, A. Rector, M. Van Ranst, P. A. Fair, G. D. Bossart, and A. B. Jenson. 2006. Journal of General Virology 87:3559-3565, which are incorporated herein by reference. With respect to cetaceans, PVs have been found in or suspected to be the agents of: genital and/or lingual tumors in Burmeister's porpoises (Phocoena spinipinnis, PsPV-1), and dusky dolphins (Lagenorhynchus obscurus) from Peru; cutaneous warts in a harbour porpoise (Phocoena phocoena) of the North Sea, and at least one killer whale (Orcinus orca, “Keiko”—captured in the North Atlantic 1983); and genital warts of sperm whales (Physeter catodon) from Icelandic waters, and of bottlenose (Tursiops truncatus) and long-beaked common dolphins (Delphinus capensis) from Peru.
The first evidence of virus-like particle (VLP)-vaccine efficacy came from a canine oral PV (COPV) system. Beagles vaccinated with VPLs generated in insect cells became completely resistant to experimental challenges with COPV. Virus-like particles (VLPs) derived from HPV-16 and -18 and used as PV vaccines have been generated in insect cells [CERVARIX™, GlaxoSmithKline (GSK), Biologicals of Rixensart, Belgium]. Similar particles derived from HPV-6, -11, -16, and -18 have been prepared for a quadrivalent vaccine in yeast (GARDASIL®, Merck & Co. of Rahway; N.J.). HPV-16 and -18 represent the most prevalent human high-risk genital PVs, together accounting for approximately 72% of cervical carcinomas, whereas HPV-6 and -11 are representatives for low-risk viruses, which cause warts in both sexes. The HPV VLP vaccines consist of the corresponding self-assembled major capsid proteins, the L1 proteins. In first trials with more than 3,000 participants involved, both vaccines prevented persistent infection of the viral types included in the vaccine for 100% of vaccinated women, and reduced cervical abnormalities by more than 90%.
A high incidence of orgenital papillomas and squamous cell carcinomas have been documented in free-ranging and captive dolphins. See Bossart, G. D., S. J. Ghim, M. Rehtanz, J. D. Goldstein, R. A. Varela, R. Ewing, P. A. Fair, R. Lenzi, B. Joseph, C. Hicks, L. Schneider, C. J. McKinnie, J. S. Reif, R. Sanchez, A. Lopez, S. Novoa, J. Bernal, M. Goretti, M. Rodriguez, R. H. Defran, and A. B. Jenson. 2005. Aquatic Mammals 31:473-480, which is incorporated herein by reference. Surgical removal of lingual and genital dolphin warts from captive animals is almost always associated with recurrence. Additionally, some of these tumors, which are believed to be caused by PVs, become malignant and spread into the brain. Accordingly, there remains a need in the art for compositions and methods for preventing or reducing transmission of TtPVs between dolphins held in the same pools (horizontal transmission) and between mothers and calves (vertical transmission).